SARS-CoV-2 Infection and Development of Islet Autoimmunity in Early Childhood
Authors: Marija Lugar, Anne Eugster, Peter Achenbach, Thekla von dem Berge, Reinhard Berner, Rachel E. J. Besser, Kristina Casteels, Helena Elding Larsson, Gita Gemulla, Olga Kordonouri, Annett Lindner, Markus Lundgren, Denise Müller, Mariusz Oltarzewski, Anne Rochtus, Marlon Scholz, Agnieszka Szypowska, John A. Todd, Anette-Gabriele Ziegler, Ezio Bonifacio, Melanie Gündert, Florian Haupt, Stefanie Arnolds, Karina Blasius, Nadine Friedl, Cigdem Gezginci, Gertrud Göppel, Martin Heigermoser, Maja Hergl, Bianca Höfelschweiger, Manja Jolink, Krisztian Kisfügedi, Nadine Klein, Claudia Matzke, Rebecca Niewöhner, Katharina Schütte-Borkovec, Andreas Weiß, José Maria Zapardiel Gonzalo, Sarah Schmidt, Merve Vurucu, Katharina Sarcletti, Melanie Sporreiter, Stefanie Jacobson, Charlien Janssen, Hilde Morobé, Brontë Vrancken, Natalie Van den Driessche, Gert Van Poel, Renka Van Heyste, Janne Houben, Veerle Vanhuyse, Sari Arabi, Lisa Barbknecht, Sevina Dietz, Franziska Ehrlich, Zahra Gholizadeh, Raphael Hoffmann, Angela Hommel, Franziska Lange, Anja Loff, Robert Morgenstern, Anne Schille, Maike Sigg, Marc Weigelt, Andre Weise, Nicole Zubizarreta , Thomas Danne, Laura Galuschka, Carolin Kruse, Sarah Landsberg, Karin Lange, Erika Marquardt, Felix Reschke, Frank Roloff, Jantje Weiskorn, Mareike Polier, Bianca Schmidt, Melanie Bunk, Anna Hofelich, Elisabeth Huber, Melina Kaiser, Alexandra Käßl, Benjamin Marcus, Annette Munzinger, Claudia Ramminger, Franziska Reinmüller, Veronika Vollmuth, Christiane Winkler, Sylwia Dybkowska, Lidia Groele, Dorota Owczarek, Katarzyna Popko, Adrianna Cieloch, Katarzyna Dzygalo, Elżbieta Górska, Agnieszka Mroczek, Beata Zduńczyk, Anna Zych, Wiktoria Czerwińska, Natalia Dziedzic, Hanna Samuelsson, Sofie Alström Mortin, Rasmus Bennet, Charlotte Brundin, Susanne Dahlberg, Lina Fransson, Ida Jönsson, Hannah Nenonen, Anita Ramelius, Carina Törn, Ulrika Ulvenhag, Marielle Lindström, Kobra Rhamati, Malin Goldman Tsubarah, Falastin Salami , Sophia Hawkins, Yama F Mujadidi, Ian Smith, Fenella Roseman, Hannah Robinson, Nazia Taj, Conor Whelan, Tabitha Wishlade, Sophie Vernon, Helen Ratcliffe
Journal: JAMA (2023)

Importance The incidence of diabetes in childhood has increased during the COVID-19 pandemic. Elucidating whether SARS-CoV-2 infection is associated with islet autoimmunity, which precedes type 1 diabetes onset, is relevant to disease etiology and future childhood diabetes trends. Objective To determine whether there is a temporal relationship between SARS-CoV-2 infection and the development of islet autoimmunity in early childhood. Design, Setting, and Participants Between February 2018 and March 2021, the Primary Oral Insulin Trial, a European multicenter study, enrolled 1050 infants (517 girls) aged 4 to 7 months with a more than 10% genetically defined risk of type 1 diabetes. Children were followed up through September 2022. Exposure SARS-CoV-2 infection identified by SARS-CoV-2 antibody development in follow-up visits conducted at 2- to 6-month intervals until age 2 years from April 2018 through June 2022. Main Outcomes and Measures The development of multiple (≥2) islet autoantibodies in follow-up in consecutive samples or single islet antibodies and type 1 diabetes. Antibody incidence rates and risk of developing islet autoantibodies were analyzed. Results Consent was obtained for 885 (441 girls) children who were included in follow-up antibody measurements from age 6 months. SARS-CoV-2 antibodies developed in 170 children at a median age of 18 months (range, 6-25 months). Islet autoantibodies developed in 60 children. Six of these children tested positive for islet autoantibodies at the same time as they tested positive for SARS-CoV-2 antibodies and 6 at the visit after having tested positive for SARS-CoV-2 antibodies. The sex-, age-, and country-adjusted hazard ratio for developing islet autoantibodies when the children tested positive for SARS-CoV-2 antibodies was 3.5 (95% CI, 1.6-7.7; P = .002). The incidence rate of islet autoantibodies was 3.5 (95% CI, 2.2-5.1) per 100 person-years in children without SARS-CoV-2 antibodies and 7.8 (95% CI, 5.3-19.0) per 100 person-years in children with SARS-CoV-2 antibodies ( P = .02). Islet autoantibody risk in children with SARS-CoV-2 antibodies was associated with younger age (&amp;amp;lt;18 months) of SARS-CoV-2 antibody development (HR, 5.3; 95% CI, 1.5-18.3; P = .009). Conclusion and relevance In young children with high genetic risk of type 1 diabetes, SARS-CoV-2 infection was temporally associated with the development of islet autoantibodies.